Heritable epigenetic variation among maize inbreds

Epigenetic variation describes heritable differences that are not attributable to changes in DNA sequence. There is the potential for pure epigenetic variation that occurs in the absence of any genetic change or for more complex situations that involve both genetic and epigenetic differences. Methylation of cytosine residues provides one mechanism for the inheritance of epigenetic information. A genome-wide profiling of DNA methylation in two different genotypes of Zea mays (ssp. mays), an organism with a complex genome of interspersed genes and repetitive elements, allowed the identification and characterization of examples of natural epigenetic variation. The distribution of DNA methylation was profiled using immunoprecipitation of methylated DNA followed by hybridization to a high-density tiling microarray. The comparison of the DNA methylation levels in the two genotypes, B73 and Mo17, allowed for the identification of approximately 700 differentially methylated regions (DMRs). Several of these DMRs occur in genomic regions that are apparently identical by descent in B73 and Mo17 suggesting that they may be examples of pure epigenetic variation. The methylation levels of the DMRs were further studied in a panel of near-isogenic lines to evaluate the stable inheritance of the methylation levels and to assess the contribution of cis- and trans- acting information to natural epigenetic variation. The majority of DMRs that occur in genomic regions without genetic variation are controlled by cis-acting differences and exhibit relatively stable inheritance. This study provides evidence for naturally occurring epigenetic variation in maize, including examples of pure epigenetic variation that is not conditioned by genetic differences. The epigenetic differences are variable within maize populations and exhibit relatively stable trans-generational inheritance. The detected examples of epigenetic variation, including some without tightly linked genetic variation, may contribute to complex trait variation.     

Growth-induced buckling of an epithelial layer

We use a proof-of-concept experiment and two mathematical models to explore growth-induced tissue buckling, as may occur in colorectal crypt formation. Our experiment reveals how growth of a cultured epithelial monolayer on a thin flexible substrate can cause out-of-plane substrate deflections. We describe this system theoretically using a ‘bilayer’ model in which a growing cell layer adheres to a thin compressible elastic beam. We compare this with the ‘supported-monolayer’ model due to Edwards and Chapman (Bull Math Biol 69:1927–1942, 2007) for an incompressible expanding beam (representing crypt epithelium), which incorporates viscoelastic tethering to underlying stroma. We show that the bilayer model can exhibit buckling via parametric growth (in which the system passes through a sequence of equilibrium states, parameterised by the total beam length); in this case, non-uniformities in cell growth and variations in cell–substrate adhesion are predicted to have minimal effect on the shape of resulting buckled states. The supported-monolayer model reveals how competition between lateral supports and stromal adhesion influences the wavelength of buckled states (in parametric growth), and how non-equilibrium relaxation of tethering forces influences post-buckled shapes. This model also predicts that non-uniformities in growth patterns have a much weaker influence on buckled shapes than non-uniformities in material properties. Together, the experiment and models support the concept of patterning by growth-induced buckling and suggest that targeted softening of a growing cell layer provides greater control in shaping tissues than non-uniform growth.     

Plasma volume restoration with salt tablets and water after bed rest prevents orthostatic hypotension and changes in supine hemodynamic and endocrine variables

Head-down bed rest changes the values of many cardiovascular and endocrine variables and also elicits significant hypovolemia. Because previous studies had not controlled for hypovolemia, it is unknown whether the reported changes were primary effects of bed rest or secondary effects of bed rest-induced hypovolemia. We hypothesized that restoring plasma volume with salt tablets and water after 12 days of head-down bed rest would result in an absence of hemodynamic and endocrine changes and a reduced incidence of orthostatic hypotension. In 10 men, we measured changes from pre-bed-rest to post-bed-rest in venous and arterial pressures; heart rate; stroke volume; cardiac output; vascular resistance; plasma norepinephrine, epinephrine, vasopressin, renin activity (PRA), and aldosterone responses to different tilt levels (0 degrees, -10 degrees, 20 degrees, 30 degrees, and 70 degrees); and plasma volume and platelet alpha2- and lymphocyte beta2-adrenoreceptor densities and affinities (0 degrees tilt only). Fluid loading at the end of bed rest restored plasma volume and resulted in the absence of post-bed-rest orthostatic hypotension and changes in supine hemodynamic and endocrine variables. Fluid loading did not prevent post-bed-rest increases in beta2-adrenoreceptor density or decreases in the aldosterone-to-PRA ratio (P = 0.05 for each). Heart rate, epinephrine, and PRA responses to upright tilt after bed rest were increased (P < 0.05), despite the fluid load. These results suggest that incidents of orthostatic hypotension and many of the changes in supine hemodynamic and endocrine variables in volume-depleted bed-rested subjects occur secondarily to the hypovolemia. Despite normovolemia after bed rest, beta2-adrenoreceptors were upregulated, and heart rate, epinephrine, and PRA responses to tilt were augmented, indicating that these changes are independent of volume depletion.